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The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.

Background/objectives The possible role of gammaaminobutyric acid (GABA) in the pathogenesis of migraine has been suggested by a number of biochemical, pharmacological, neurophysiological and experimental data. We investigated the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptor rho1, 2, and 3 genes (GABRR1, GABRR2, and GABRR3) and the risk of developing migraine. Methods The frequency of GABRR1 rs12200969, GABRR1 rs1186902, GABRR2 rs282129, and GABRR3 rs832032 genotypes and allelic variants were studied in a case-control association study involving 197 patients with migraine and 278 healthy controls by means of a TaqMan-based qPCR Assay. We also studied the possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes. Results The frequencies of the genotypes and allelic variants of the 4 SNPs were similar in migraine patients and controls. Gender, positive family history of migraine, presence or absence of aura, and triggering of migraine attacks by ethanol did not influence the frequency of these genotypes. Carriers of the minor allele of the rs1186902 SNP showed a trend towards later onset of migraine. Conclusion The most common polymorphisms in the GABRR genes seemed to be not associated with the risk for migraine in Caucasian Spanish people, although one of them (GABRR1 rs1186902) shows a statistically significant association with the age of onset of migraine.

Background/Objectives Many biochemical, pharmacological, neuropathological, and experimental data suggest a possible role of nitric oxide in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the neuronal nitric oxide synthase gene (NOS1 or nNOS; chromosome 12q24.22) and the risk for migraine. Methods We studied the frequency of the of rs7977109 and rs693534 genotypes and allelic variants in 197 patients with migraine and 308 healthy controls using a TaqMan-based qPCR assay. As a secondary analysis, we studied the possible influence of gender, age at onset of migraine, positive family history of migraine, and presence or absence of aura on the genotypes frequency. Results The frequencies of rs7977109 and rs693534 genotypes and allelic variants were not associated with the risk for migraine with OR for minor alleles = 0.94 (95% CI 0.72-1.23) and = 0.88 (0.68-1.15), respectively, and the lack of association was not influenced by gender, age at onset of migraine, positive family history of migraine, and presence or absence of aura. Conclusion NOS1 rs7977109 and rs693534 genotypes and allelic variants are not associated with the risk for migraine in Caucasian Spanish people.

Several biochemical, pharmacological, neurophysiological and experimental data suggest a possible role of gamma-aminobutyric acid (GABA) in the pathogenesis of migraine. We investigated the possible association of the most common single nucleotide polymorphisms (SNPs) in the GABA receptor alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) genes with the risk for migraine. A TaqMan-based qPCR assay designed to detect the most common SNPs in the GABRA4 (rs2229940), GABRE (rs1139916), and GABRQ (rs3810651) was performed in 197 migraine patients and 394 age- and gender-matched controls. The possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes was also studied. The frequency of GABRE rs1139916AA genotype was significantly lower in the migraine group only in the female gender, but the differences did not reach statistical significance after correction for multiple comparisons. The mean ± SD age at onset of migraine was significantly lower in patients with GABRQ rs3810651AA as compared with the other two genotypes. Positive family history of migraine and presence or absence of aura did not influence the frequencies of the genotypes of the three SNPs studied. Triggering of migraine by ethanol was significantly less frequent in patients with GABRA4 rs2229940GG and more frequent in patients with GABRQ 3810651TT genotype, but the differences lost statistical significance after correction for multiple comparisons. GABRQ rs3810651 could play a role in the modification of age at onset of migraine.

Background/objectives Glutamate has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism rs3794087 in the SLC1A2 gene ( EATT2 or GLT-1; chromosome 11p13-p12 involved in glutamate transport) and the risk for migraine and for triggering migraine attacks by alcohol. Methods We studied the frequency of the rs3794087 genotypes and allelic variants in 197 patients with migraine and 308 healthy controls using a TaqMan -based qPCR assay. Results The frequencies of the rs3794087 genotypes and alleles were similar in patients with migraine and controls, and were unrelated with the age of onset of migraine, gender, presence or absence of aura, or family history of migraine Conclusion rs3794087 genotype and allelic variants were not related with the risk for migraine in Caucasian Spanish people.

A recent meta-analysis suggests an association between the rs11558538 single nucleotide polymorphism in the histamine-N-methyl-transferase (HNMT) gene and the risk for Parkinson’s disease. Based on the possible relationship between PD and restless legs syndrome (RLS), we tried to establish whether rs11558538 SNP is associated with the risk for RLS. We studied the genotype and allelic variant frequencies of HNMT rs11558538 SNP 205 RLS patients and 410 healthy controls using a TaqMan assay. The frequencies of the HNMT rs11558538 genotypes allelic variants were similar between RLS patients and controls, and were not influenced by gender, family history of RLS, or RLS severity. RLS patients carrying the genotype rs11558538TT had an earlier age at onset, but this finding was based on three subjects only. These results suggest a lack of major association between HNMT rs11558538 SNP and the risk for RLS.

Mutations in the microtubule-associated protein tau gene (MAPT) can cause frontotemporal dementia with Parkinsonism linked to the chromosome 17, and are associated with the risk for progressive supranuclear palsy, Parkinson's disease, corticobasal degeneration, and multiple system atrophy. We tried to establish, whether MAPT H1 discriminating haplotype single nucleotide polymorphisms (SNP) (rs1052553) is associated with the risk for restless legs syndrome (RLS). We studied the allelic and genotype frequencies of the SNP rs1052553 in 205 patients with RLS and 324 healthy controls using TaqMan genotyping. rs1052553 genotype and allelic frequencies did not differ significantly between patients with RLS and controls, and were unrelated with the age at onset of RLS, gender, family history of RLS, and severity of RLS. The results of the present study suggest that the SNP rs1052553 is not related with the risk for RLS.

Background/objectives Slowing of motor performance in human aging is a well demonstrated clinical observation. Information on the influence of gender in motor performance is less well-established. With the aim of analyzing the possible influence of age and gender in motor performance, we studied basic motor function in a large series of healthy sex-matched individuals aged > 40 years. Methods We studied 246 subjects (123 males and 123 females; mean age 63.67 ± 10.79 and 63.61 ± 11.04 years, respectively), stratified by age in 7 groups for each gender. Evaluation included four timed tests (pronation–supination, finger tapping and movement between two points, all with both hands, and walking test), and the three tests performed on a personal computer (speed for pressing repetitively a key — frequency, visual reaction time and movement time, all with both hands). Statistical analysis included two-way analysis of variance (ANOVA) for two factors (age and gender) and Pearson's or Spearman's correlation tests where appropriate. Results The analysis of motor performance between subgroups showed a clear influence of age on motor performance of all the tests, with the exception of the left visual reaction time. The results of all the motor tests performed were inversely correlated with age. Gender influenced the performance (the speed of motor performance was significantly better in males) of all the tasks with the exception of left pronation–supination, and left and right visual reaction time. Conclusion Our results confirm in a large series of healthy subjects that basic motor performance deteriorates with age and is influenced by gender.

Objective A glutamatergic dysfunction has been postulated to play a role in restless legs syndrome (RLS) pathophysiology, as glutamate concentrations have been found to increase in the thalamus of RLS patients. The aim of our study was to investigate the possible association between the single nucleotide polymorphism (SNP) rs3794087 in the solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2 , related with glutamate transport and the risk for RLS. Methods We studied the allelic and genotype frequencies of the SNP rs3794087 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. Results The rs3794087 genotype and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, and family history of RLS. Conclusions The results of our study suggest that the rs3794087 polymorphism is not related to the risk for RLS.

(Headache 2010;50:85-91) Background/Objectives.— Alcohol has been traditionally considered a possible migraine trigger factor. Alcohol-dehydrogenase (ADH) enzymes are thought to play important roles in the metabolism of ethanol. Relevant polymorphism has been found only for 2 of the ADH genes (mapped on chromosome ): ADH 1B, betapolypeptide (ADH2) and ADH3. The polymorphism rs1229984, located in the third exon of the human ADH2 gene, causes the amino acid substitution Arg48His. The aim of this study was to investigate the possible association between ADH2 polymorphism and the risk for migraine and for triggering migraine attacks. Methods.— We studied the frequency of the ADH2 genotypes and allelic variants in 197 patients with migraine and 255 healthy controls using allele-specific PCR amplification and MslI-RFLP's analyses. Results.— The frequencies of ADH2 Arg/His genotype and of ADH2 His allele were significantly lower in patients with migraine when compared with those of controls, and were unrelated with the age of onset of migraine attacks, family history of migraine or presence of aura. The frequency of the allelic variant ADH2 His (ADH2*2) was significantly higher in the group of patients who reported triggering of migraine by alcohol when compared with the group who reported no effect. Conclusion.— The results of the present study suggest that ADH2 Arg/His genotype should be associated with a decreased risk for migraine, while the ADH2 His allelic variant should be related with the risk for triggering migraine attacks after alcohol consumption in our population of migraine patients.

Background.—Histamine has been implicated in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the diamine oxidase gene (DAO; chromosome 7q36.1, involved in histamine metabolism) and the risk for migraine. Methods.—We studied the frequency of the rs2052129, rs10156191, rs1049742, and rs1049793 genotypes and allelic variants in 197 patients with migraine and 245 healthy controls using a TaqMan-based qPCR Assay. Results.—The DAO SNP rs10156191, which is related to decreased DAO enzyme activity, is associated with the risk of developing migraine, particularly in women. The odds ratio (OR) for the defect allele positivity is 1.61 (95% confidence interval 1.31-2.37) for overall migraine patients and 2.08 (1.29-3.36) for women suffering from migraine. The association was not influenced by confounders such as the age at onset, the presence of aura, positivity of alcohol as a triggering factor, positive family history of aura, or family history of allergy. Multiple regression analyses did not confirm association with the rest of genetic factors. Conclusion.—Our findings, which should be framed as hypothesis generating, suggest that DAO genotypes and allelic variants are associated with the risk for migraine in Caucasian Spanish people, especially in women.

Spontaneous intracranial hypotension (SIH) is a rare syndrome characterized by postural headache associated with a low cerebrospinal fluid pressure in the absence of dural puncture or penetrating trauma. Cranial magnetic resonance imaging (MRI) typically shows diffuse pachymeningeal gadolinium enhancement, subdural fluid collections, prominence of cerebral venous sinuses and brain descent. Visual signs and symptoms have been described infrequently in patients with SIH. These include third or sixth nerve palsy, superior nasal quadrantanopia and temporal hemianopia. We report a 34 year-old woman who presented with a two-year history of orthostatic headache, dizziness and transient visual obscurations. Campimetry showed a bilateral concentric visual field defect. She also described that intermittently a transparent fluid leaked out of her nose. She had no past history of trauma, sinus surgery or intracranial surgery. Cranial MRI was normal. Neuro-ophthalmological examination ruled out any other causes of concentric visual field defects. Lumbar puncture showed a cerebrospinal fluid (CSF) opening pressure of 9 cm H2O. Radioisotope cisternography suggested a dural leak at cribiform plate. The cribiform plate region was repaired endoscopically with improvement of all symptoms. One year later she remains asymptomatic and the visual field defects have improved.

The possible usefulness of botulinum toxin type A in the treatment of bruxism has not been studied exhaustively, being limited to some isolated case reports, two short case-series and a double-blind study involving a small number or patients. This article report our long-term experience in the treatment of bruxism with botulinum toxin type A.The outcome of 19 patients with severe bruxism who underwent periodical treatment with botulinum toxin A infiltrations in both temporal and masseter muscles, using initial doses of 25 IU per muscle, during a follow-up period ranging from 0.5 to 11 years, is described. Doses were adjusted in follow-up visits according the response degree.None of the patients reported side-effects. Final doses ranged from 25 to 40 IU per muscle (mean: 29.7 ± 4.9 UI), and duration of the effect from 13 to 26 weeks (mean: 16.7 ± 5.1 weeks).Botulinum toxin A infiltrations are a safe and useful treatment for patients with severe bruxism.

Background/objectives: Dopamine has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism 312G>A (rs6280) in the DRD3 gene(essential tremor 1-ETM1- locus, chromosome 3q13) and the risk for migraine and for triggering migraine attacks by alcohol. Methods: We studied the frequency of the DRD3 genotypes and allelic variants in 197 patients with migraine and 282 healthy controls using a polymerase chain reaction and MlsI-restriction fragment length polymorphisms method. Results: The frequencies of the DRD3 genotypes and DRD3Gly9 were similar in patients with migraine and controls and were unrelated to the age of onset of migraine, gender, family history of migraine and triggering of migraine attacks by alcohol. The frequency of the genotype DRD3Gly9Gly9 was significantly higher in patients with migraine with aura when compared with patients with migraine without aura, but not with controls. Conclusion: DRD3 genotype and allelic variants were not related to the risk for migraine in Caucasian Spanish people.

The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by the gene PON1 (chromosome 7q21.3) plays a role as an antioxidant molecule through several mechanisms. Because oxidative stress has been implicated in the pathogenesis of migraine, we have investigated the possible association between the nonsynonymous polymorphisms 55LM and 192QR in the PON1 and the risk for migraine. We studied the frequency of the PON1 genotypes and allelic variants in 197 patients with migraine and 220 healthy controls using a TaqMan single nucleotide polymorphism analysis. The frequencies of the PON1 genotypes and PON1 allelic variants did not differ significantly between patients with migraine and controls, and were unrelated with gender, family history of migraine, and presence or absence of aura. The frequencies of the genotype PON1 192QQ and the allelic variant PON1 192Q were significantly higher in patients with earlier onset of migraine. The results of the present study suggest that PON1 polymorphisms are not related with the risk for migraine in Caucasian Spanish people, although PON1 192Q/Q genotype and PON1 192Q allelic variant should be related with an earlier onset of migraine.

Background/Objectives.— Histamine has been implicated in the pathogenesis of migraine. In the CNS, histamine is almost exclusively metabolized by the polymorphic enzyme histamine N-methyltransferase (HNMT). The HNMT gene (chromosome 2q22.1), shows diverse single nucleotide polymorphisms. One of these, located in exon 4 C314T, causes the amino acid substitution Thr105Ile, related to decreased enzyme activity. The aim of this study was to investigate the possible association between HNMT polymorphism and the risk for migraine. Methods.— We studied the frequency of the HNMT genotypes and allelic variantes in 197 patients with migraine and 245 healthy controls using a PCR-RLFP method. Results.— The frequencies of the HNMT genotypes and allelic variants did not differ significantly between migraine patients and controls, and were unrelated with the age of onset of migraine attacks, gender, personal history of allergic diseases, family history of migraine, or presence of aura. Conclusion.— The results of the present study suggest that HNMT polymorphism in not related with the risk for migraine.

Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls. The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs. The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.